Survival rates for preterm infants have improved dramatically in recent decades due to advances in perinatal and neonatal care. However long term neurodevelopmental outcomes have not improved and remain a major public heath concern. Neuroimaging of preterm infants whilst in the neonatal intensive care unit (NICU) could provide early recognition of cerebral injury resulting in subsequent neurodevelopmental disability and insight into the timing and pathogenetic factors associated with such regional cerebral functional deficits. An emerging neuroimaging modality, diffuse optical imaging (DOI), uses near-infrared light spectroscopy (NIRS) to non-invasively map changes in cerebral blood oxygenation and volume in response to neural activity. For preterm infants, DOI has the advantages of portability for use at the bedside in the NICU, and comprehensive hemoglobin imaging contrasts for characterizing immature neurovascular coupling. To date, however, the clinical application of DOI has been limited by technological challenges. Previous DOI systems did not meet stringent instrumentation requirements resulting in limited spatial resolution and confounds due to superficial signals arising from the scalp and skull. We have recently developed a new high-performance diffuse optical tomography (DOT) system that overcomes these challenges and provides significant improvements in resolution and signal discrimination. Our ultimate goal is the detection of preterm infant cerebral functional deficits and the pathophysiology related to such deficits through comparison of brain function maps both within preterm infants and to control healthy term infants. In this exploratory R21 grant, we will establish new DOI neuroimaging techniques in preparation for the subsequent multi-year longitudinal studies focused on understanding the trajectory of neuorological deficits in preterm infants. Specifically, high-performance DOI methods will be extended for application in infants (Aim 1). Age-specific neuroimaging protocols will be developed for preterm and term infants (Aim 2). Using the optimized DOI methods and imaging protocols, an exploratory study of preterm and term infants will evaluate the altered brain function of preterm infants with and without brain injury. The maps of preterm brain function will be analyzed for longitudinal changes (at 40 and 48 weeks of age) and for correlations with brain injury (Aim 3). PUBLIC HEALTH RELEVANCE: This grant aims to establish diffuse optical imaging (DOI) techniques for mapping the development of cerebral function in preterm infants. DOI has the advantages of portability for use at the bedside in the neonatal intensive care unit (NICU) and comprehensive hemoglobin imaging contrasts for characterizing immature brain physiology. Functional neuroimaging of preterm infants during the NICU course may provide early recognition of specific patterns of neurological deficits, as well as insight into pathogenetic pathways in these high risk infants.